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Abstract Nickel(Ni)-containing materials have been widely used in a wide range of medical applications, including orthopaedics. Despite their excellent properties, there is still a problem with the release of nickel ions into the patient’s body, which can cause changes in the behaviour of surrounding cells and tissues. This study aims to evaluate the effects of Ni on bone cells with an emphasis on the determination of Ni localization in cellular compartments in time. For these purposes, one of the most suitable models for studying the effects induced by metal implants was used—the patient’s osteoarthritic cells. Thanks to this it was possible to simulate the pathophysiological conditions in the patient’s body, as well as to evaluate the response of the cells which come into direct contact with the material after the implantation of the joint replacement. The largest differences in cell viability, proliferation and cell cycle changes occurred between Ni 0.5 mM and 1 mM concentrations. Time-dependent localization of Ni in cells showed that there is a continuous transport of Ni ions between the nucleus and the cytoplasm, as well as between the cell and the environment. Moreover, osteoarthritic osteoblasts showed faster changes in concentration and ability to accumulate more Ni, especially in the nucleus, than physiological osteoblasts. The differences in Ni accumulation process explains the higher sensitivity of patient osteoblasts to Ni and may be crucial in further studies of implant-derived cytotoxic effects.

An adjectival simile is an established phraseological unit with a standardised form (blind as a bat). It is perhaps for this reason that it has not been attracting much attention, and most studies on similes focus on verbal similes. This study reports a significant diachronic shift in the usage of adjectival similes, identified by comparing a lexicographic sample with one from a corpus. Analysing corpus data, we collected a representative sample of 309 adjectival similes in English, which further served for the compilation of a “simile minimum” of 60 types. Both corpus samples were then contrasted with lexicographic lists from a dictionary of idioms: English Idioms and How to Use Them (Seidl & McMordie, 1978; 1988). The comparison shows that the lexicographic minimum (65 types) overlaps with that from the corpus by just one-third and the whole representative list (166 types) only by one-fifth. The significant disproportion can be explained as a shift in linguistic reality but also as a result of the dictionary authors’ idiolects or homogeneity of their data. These findings can serve for textbook and reference manual authors as a warning against relying too much on their own linguistic intuition.

This issue of the Weizenbaum Journal of the Digital Society addresses the increasing prevalence of algorithmic management in both business and public administration. This subject is the focus of vigorous debate across sociology, law, political science, and economics. The articles featured in this issue not only analyse the historical foundations of this practice but also examine its manifestations in various contexts, extending beyond the gig economy to encompass other industries.

Abstract Inflammasome assembly is a potent mechanism responsible for the host protection against pathogens, including viruses. When compromised, it can allow viral replication, while when disrupted, it can perpetuate pathological responses by IL-1 signaling and pyroptotic cell death. SARS-CoV-2 infection was shown to activate inflammasome in the lungs of COVID-19 patients, however, potential mechanisms responsible for this response are not fully elucidated. In this study, we investigated the effects of ORF3a, E and M SARS-CoV-2 viroporins in the inflammasome activation in major populations of alveolar sentinel cells: macrophages, epithelial and endothelial cells. We demonstrated that each viroporin is capable of activation of the inflammasome in macrophages to trigger pyroptosis-like cell death and IL-1α release from epithelial and endothelial cells. Small molecule NLRP3 inflammasome inhibitors reduced IL-1 release but weakly affected the pyroptosis. Importantly, we discovered that while SARS-CoV-2 could not infect the pulmonary microvascular endothelial cells it induced IL-1α and IL-33 release. Together, these findings highlight the essential role of macrophages as the major inflammasome-activating cell population in the lungs and point to endothelial cell expressed IL-1α as a potential novel component driving the pulmonary immunothromobosis in COVID-19.

Abstract Background Recent developments suggest that neurosteroids may achieve rapid antidepressant effects. As such, neurosteroidogenesis mediated by the translocator protein 18 kDa (TSPO) might constitute a promising option for the treatment of depression. Therefore, the current clinical trial aims to get the first evidence of whether TPSO ligands promote rapid antidepressant effects. Furthermore, we study which mechanisms of action, e.g., modulation of distinct neuronal networks, neurosteroidogenesis, endocrinological mechanisms, TSPO expression or microbiome composition, contribute to their putative antidepressant effects. Methods This is a randomized, placebo-controlled, double-blind single-center trial of 2-week treatment with the TSPO ligand etifoxine versus placebo in depressive patients. Main eligibility criteria: male or female individuals aged 18 to 65 years with unipolar/bipolar depressive disorder with no other psychiatric main diagnosis or acute neurological/somatic disorder or drug/alcohol dependence during their lifetime. The primary endpoint is the time point at which 50% of the maximal effect has occurred (ET50) estimated by the scores of the Hamilton Depression Scale (HAMD-21). A total of 20 patients per group are needed to detect changes of therapeutic efficacy about 5% and changes of ET50 about 10% with a power of 70%. Assuming a drop-out rate of 10–20%, 50 patients will be randomized in total. The study will be conducted at the Department of Psychiatry and Psychotherapy of the University of Regensburg. Discussion This study will provide a first proof-of-concept on the potential of the TSPO ligand etifoxine in the treatment of depressive disorders. Trial registration Clinical Trials Register (EudraCT number: 2021-006773-38 , registration date: 14 September 2022) and German Register of Clinical Studies (DRKS number: DRKS00031099 , registration date: 23 January 2023).

The shift of instruction imposed on higher education institutions by the pandemic-related restrictions bolstered the interest in students' online class participation. This study investigates university students' engagement in remote foreign language classes during the COVID-19 lockdown. While engagement is a multi-faceted construct, we only aim to explore its behavioural dimension. The authors felt compelled to acknowledge and comprehend their students' behaviour in contingency online learning (COL). Through a qualitatively oriented exploratory case study, we sought to answer two research questions related to the extent the use of technical equipment and remote physical environment influenced students' engagement. The study was conducted with students enrolled in regular, in-person Bachelor's or Master's degree courses to qualify as teachers of English at primary or lower-secondary schools. The results indicate that the use of technology did not prove to be a significant obstacle to online learning engagement. Concerning the remote physical environment, the learning process was compromised most significantly by the intimate character of the home-working space. We believe that our findings will help educators to rationalise their expectations and formulate best practice recommendations.

The understanding of analytical chemistry and its application in different areas of life science is something that should be encouraged for students studying chemistry, and also something that appeals to many students. Life science includes a vast variety of areas, out of which some are more easily approached in student projects. The chemical communication between organisms, such as plants, as described in chemical ecology is one example. It is therefore beneficial to offer students inquiry-based project work that allows them to explore, and gain a deeper understanding of, this discipline within the grand context that is chemistry. Hence, the present work describes the application of analytical chemistry using gas chromatography--mass spectrometry, including sample preparation for the study of chemical inhibitory (allelopathic) properties of compounds found in the plant "Aegopodium podagraria." The questions posed to the students performing this project work were "What compounds can be found in the extracts of the plant?", "Are the extracts allelopathic?", and "Can you determine which compounds contribute to the possible allelopathic properties?". The reported results indicate that the extracts might have allelopathic properties and showed that the extracts contained compounds such as a-pinene and ß-caryophyllene. The identified terpenes were shown to have minor allelopathic properties by themselves but displayed an impact on the germination of seeds and length of the sprouts when applied as a blend. This project, and its results, proposes a framework for investigation of other plants and can be adapted to suit students at different academic levels.

BackgroundThe hepatitis E virus (HEV) can cause acute viral hepatitis with or without neurological manifestations, and occasionally progresses to chronic infection in immunocompromised individuals. The management of chronic HEV infection in cancer patients may be challenging due to the complex immunological constellation. Furthermore, the diagnostic workflow and the impact on quality of life of neurological HEV manifestations in immunocompromised patients have not been sufficiently delineated previously.Case descriptionA 61-year-old male with systemically treated chronic lymphocytic leukemia (CLL) experienced a slowly progressive atrophy of the spinal cord due to a chronic HEV infection. Despite continuous antiviral treatment with ribavirin, the patient’s neurological condition continued to deteriorate, particularly following subsequent attempts to treat CLL. Treatment with obinutuzumab resulted in acute bowel and urinary retention and a further deterioration of motor skills, prompting the discontinuation of obinutuzumab. The patient’s neurological status improved after the administration of intravenous immunoglobulins.ConclusionThis case study provides a comprehensive long-term follow-up of a cancer patient with chronic HEV infection and associated CNS involvement, which resulted in progressive neurological disability over several years. The challenges faced in diagnosing new neurological symptoms in patients undergoing immunosuppressive cancer treatment underscore the need for an interdisciplinary diagnostic approach that includes HEV testing. We propose a diagnostic pathway for future validation in immunocompromised cohorts presenting with neurological symptoms, emphasizing its potential to enhance clinical outcomes.

In the spring of 2020, the University of South Bohemia was one of the innumerable higher education institutions which was obliged to move its instruction online in order to comply with the COVID-19 regulations. This article explores the evaluation of emergency remote teaching (ERT) measures taken by the English department from the perspective of its students. It presents and discusses findings gathered from a questionnaire completed by 99 respondents. The questionnaire centres around four areas of interest: satisfaction with ERT, comparison of face-to-face (F2F) vs. online learning experiences, perceived stress level during ERT, and acquisition of skills. The results show how students responded to the emergency procedures and which factors they considered essential in terms of satisfaction and stress. Furthermore, they reveal thought-provoking insights on aspects such as integrating elements of online teaching into F2F instruction, developing various skills in lockdown, and motivation for learning. Our findings are analysed in terms of aspects and factors which are viewed as efficient or inefficient by students in a time of crisis. Thus, this research may contribute not only to better preparedness should circumstances requiring ERT return, but also to a more complex re-evaluation of instructional approach at university level.

Abstract As the world’s glaciers recede in response to a warming atmosphere, a change in the magnitude and frequency of related hazards is expected. Among the most destructive hazards are glacier lake outburst floods (GLOFs), and their future evolution is concerning for local populations and sustainable development policy. Central to this is a better understanding of triggers. There is a long‐standing assumption that earthquakes are a major GLOF trigger, and seismic activity is consistently included as a key hazard assessment criterion. Here, we provide the first empirical evidence that this assumption is largely incorrect. Focusing on the Tropical Andes, we show that, of 59 earthquakes (1900–2021) the effects of which intersect with known glacier lakes, only one has triggered GLOFs. We argue that, to help develop climate resilient protocols, the focus for future assessments should be on understanding other key GLOF drivers, such as thawing permafrost and underlying structural geology.

Background and purposeBenefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice.MethodsWe used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic.ResultsWe included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (

Erectile dysfunction (ED), the impairment of achieving and maintaining an erection for satisfactory sexual intercourse, is a common pathology that men experience for a variety of different factors. Conservative treatment for ED includes changing medications, lifestyle modifications, and psychotherapy. Pharmaceutical and nonsurgical interventions include phosphodiesterase-5 inhibitors(PDE-5i), intracavernosal medication injections, and vacuum devices. Surgical treatment options for ED have evolved over time and currently include the use of inflatable penile prosthesis (IPP) and malleable penile prosthesis. IPP insertion is usually met with good patient satisfaction. However, complications of device insertion can include corporal perforation, urethral injury, cylinder erosion or extrusion, infection, and mechanical failure, to name a few. Our patient presented with device malfunction and intraoperative assessment showed the IPP tubing twisted at the levels of the reservoir on the first operation and the level of the cylinder and scrotal pump on the second operation. The twisting of the tubing resulted in a nonfunctioning IPP as the fluid was unable to fill the cylinders resulting in an erection. The patient was managed with complete device explanation and reinsertion of a new three-piece IPP per the patient and partner’s request. This is the first case report highlighting this specific complication, and we hope to provide clinicians with the resources to recognize this rare complication.

Summary: Respiratory influenza A virus (IAV) infections are major health concerns worldwide, where bacterial superinfections substantially increase morbidity and mortality. The underlying mechanisms of how IAV impairs host defense remain elusive. Macrophages are pivotal for the innate immune response and crucially regulate the entire inflammatory process, occurring as inflammatory M1- or pro-resolving M2-like phenotypes. Lipid mediators (LM), produced from polyunsaturated fatty acids by macrophages, are potent immune regulators and impact all stages of inflammation. Using LM metabololipidomics, we show that human pro-resolving M2-macrophages respond to IAV infections with specific and robust production of prostaglandin (PG)E2 along with upregulation of cyclooxygenase-2 (COX-2), which persists after co-infection with Staphylococcus aureus. In contrast, cytokine/interferon production in macrophages was essentially unaffected by IAV infection, and the functionality of M1-macrophages was not influenced. Conclusively, IAV infection of M2-macrophages selectively elevates PGE2 formation, suggesting inhibition of the COX-2/PGE2 axis as strategy to limit IAV exacerbation.